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Biomedical subjects

H Heinzl

Publications and source records attributed to H Heinzl.

At least 19 recordsLinked to original sources

Position dependent changes of cerebral blood flow velocities in premature infants.

UNLABELLED: The supine or prone positioning of infants has been a cause of much controversy. Recently it has been postulated that the position dependent hypoperfusion of the brainstem represents a possible cause of sudden infant death. To demonstrate position dependency and maturational changes of cerebral perfusion in premature newborn infants we investigated cerebral blood flow velocities (CBFV) in the main supratentorial and brainstem cerebral arteries. Measurements of CBFV were done with transfontanellar colour-coded Doppler sonography in the internal carotid artery (ICA), basilar artery (BA), and vertebral artery (VA) in the prone (head centered-baseline) and supine positions (maximal rotation to both sides) in 23 premature infants aged between 3-5 days of life. We performed follow-up measurements in 17 infants 7-10 days later and in 16 infants at the corrected age of 1 month. There was no difference in mean CBFVs between the prone and supine position at the first investigation. At the third investigation, CBFVs were significantly higher in the supine compared to the prone position. The CBFVs of the ICA were higher than in the BA and VA. This difference was not influenced by the body position but increased with post-natal age more in the VA (159%) than in the BA (129%) and ICA (128%). Position dependency was not seen in the ICA perfusion. In the prone position, five infants showed an incomplete steal effect in the contralateral VA. There was no significant side difference in the CBFVs of the ICA and VA, but in the resistance indices in the VA (left > right). CONCLUSION: in premature newborns, position dependent changes of cerebral blood flow velocity develop with maturation and are most pronounced in the vertebrobasilar system. These changes are possibly due to compression of the vertebral artery by neck movement and suggest an individual risk of brainstem perfusion deficits that may be aggravated with age and head rotation in a prone position.

Analysis of Variance↗

BJ: an S-Plus program to fit linear regression models to censored data using the Buckley-James method.

Most researchers are familiar with ordinary multiple regression models, most commonly fitted using the method of least squares. The method of Buckley and James (J. Buckley, I. James, Linear regression with censored data, Biometrika 66 (1979) 429-436.) is an extension of least squares for fitting multiple regression models when the response variable is right-censored as in the analysis of survival time data. The Buckley-James method has been shown to have good statistical properties under usual regularity conditions (T.L. Lai, Z. Ying, Large sample theory of a modified Buckley-James estimator for regression analysis with censored data, Ann. Stat. 19 (1991) 1370-1402.). Nevertheless, even after 20 years of its existence, it is almost never used in practice. We believe that this is mainly due to lack of software and we describe here an S-Plus program that through its inclusion in a public domain function library fully exploits the power of the S-Plus programming environment. This environment provides multiple facilities for model specification, diagnostics, statistical inference, and graphical depiction of the model fit.

Data Interpretation, Statistical↗

Extracting a statistical data matrix from electronic patient records.

This paper describes the processing and transformation of medical data from a clinical database to a statistical data matrix. Precise extraction and linking tools must be available for the desired data to be processed for statistical purposes. We show that flexible mechanisms are required for the different types of users, such as physicians and statisticians. In our retrieval tools we use logical queries based on operands and operators. The paper describes the method and appliance of the operators with which the desired matrix is created through a process of selection and linking. Examples with a Kaplan-Meier function and time-dependent covariables demonstrate how our model is useful for different user groups.

Biometry↗

Improved prediction of intraocular lens power using partial coherence interferometry.

PURPOSE: To evaluate the feasibility of using a new optical biometry technique, dual-beam partial coherence interferometry (PCI), to improve intraocular lens (IOL) power prediction in cataract surgery. SETTING: Department of Ophthalmology, Vienna General Hospital, and Institute of Medical Physics, University of Vienna, Vienna, Austria. METHODS: Preoperative axial length (AL) data obtained with PCI biometry and applanation ultrasound (US) biometry in 77 eyes of 51 patients was applied to 4 commonly used IOL power formulas. The refractive outcome and the mean absolute error (MAE) were calculated for each formula using both biometry methods. A linear multiple-regression model based on preoperative PCI biometry data was derived to predict the postoperative anterior chamber depth (ACD). The predictive power of this regression model was assessed by adding the predicted ACD to the SRK/T formula. Predicted residuals were calculated to evaluate the feasibility and stability of this modified IOL power formula. RESULTS: Using PCI instead of US biometry significantly improved the refractive outcome with all 4 IOL power formulas. The Holladay I and SRK/T formulas yielded an MAE of 0.44 diopter (D) using PCI AL data and 0.56 D and 0.57 D, respectively, using US biometry data. The SRK/T formula combined with the PCI regression model for postoperative ACD prediction performed slightly better (MAE 0.42 D) than the conventional SRK/T formula alone. Predicted residuals revealed an MAE of 0.46 D, proving the predictive performance of the new formula. CONCLUSIONS: Partial coherence interferometry biometry applied to several widely used IOL power formulas yielded significantly better IOL power prediction and therefore refractive outcome in cataract surgery than US biometry. Further improvement can be achieved by applying PCI to a modified SRK/T formula that predicts the postoperative ACD using PCI biometry data.

Biometry↗

A note on R2 measures for Poisson and logistic regression models when both models are applicable.

The aim of many epidemiological studies is the regression of a dichotomous outcome (e.g., death or affection by a certain disease) on prognostic covariables. Thereby the Poisson regression model is often used alternatively to the logistic regression model. Modelling the number of events and individual outcomes, respectively, both models lead to nearly the same results concerning the parameter estimates and their significances. However, when calculating the proportion of explained variation, quantified by an R2 measure, a large difference between both models usually occurs. We illustrate this difference by an example and explain it with theoretical arguments. We conclude, the R2 measure of the Poisson regression quantifies the predictability of event rates, but it is not adequate to quantify the predictability of the outcome of individual observations.

Adult↗

Influence of aortic blood flow velocity on changes of middle cerebral artery blood flow velocity during isoflurane and sevoflurane anaesthesia.

BACKGROUND AND OBJECTIVE: We studied the influence of systemic (aortic) blood flow velocity on changes of cerebral blood flow velocity under isoflurane or sevoflurane anaesthesia. METHODS: Forty patients (age: isoflurane 24-62 years; sevoflurane 24-61 years; ASA I-III) requiring general anaesthesia undergoing routine spinal surgery were randomly assigned to either group. Cerebral blood flow velocity was measured in the middle cerebral artery by transcranial Doppler sonography (depth: 50-60 mm). Systemic blood flow velocity was determined by transthoracic Doppler sonography at the aortic valve. Heart rate, arterial pressure, arterial oxygen saturation and body temperature were monitored. After standardized anaesthesia induction (propofol, remifentanil, vecuronium) sevoflurane or isoflurane were used as single agent anaesthetics. Cerebral blood flow velocity and systemic blood flow velocity were measured in the awake patient (baseline) and repeated 5 min after reaching a steady state of inspiratory and end-expiratory concentrations of 0.75, 1.00, and 1.25 mean alveolar concentrations of either anaesthetic. To calculate the influence of systemic blood flow velocity on cerebral blood flow velocity, we defined the cerebral-systemic blood flow velocity index (CSvI). CSvI of 100% indicates a 1:1 relationship of changes of cerebral blood flow velocity and systemic blood flow velocity. RESULTS: Isoflurane and sevoflurane reduced both cerebral blood flow velocity and systemic blood flow velocity. The CSvI decreased significantly at all three concentrations vs. 100% (isoflurane/sevoflurane: 0.75 MAC: 85 +/- 25%/81 +/- 23%, 1.0 MAC: 79 +/- 19%/74 +/- 16%, 1.25 MAC: 71 +/- 16%/79 +/- 21%; [mean +/- SD] P = 0.0001). CONCLUSIONS: The reduction of the CSvI vs. 100% indicates a direct reduction of cerebral blood flow velocity caused by isoflurane/sevoflurane, independently of systemic blood flow velocity.

Adult↗

A long-term review of the treatment of patients with Ewing's sarcoma in one institution.

AIMS: The treatment of patients suffering from Ewing's sarcoma has changed over the last three decades. We report the analyses, significant prognostic factors, interdisciplinary approach and development of therapy in one institution in Austria. METHODS: One hundred and forty-two patients treated for Ewing's sarcoma between 1949 and 1994 were reviewed. Median follow-up was 8.5 years. Fifty-six patients were treated between 1949 and 1980 (group 1), and 86 patients between 1981 and 1994 (group 2). Patients in group 1 were treated with polychemotherapy. Patients in group 2 were treated with a neoadjuvant CESS (Cooperative Ewing's Sarcoma Study) regimen. In group 1, 24 patients underwent biopsy only, 32 patients had a definitive operation, 48 patients received either radiation therapy only or additional radiation therapy compared with in group 2: 6, 80 and 44 cases, respectively. RESULTS: Five-year overall survival (OS) increased from 27% to 57%. Significant prognostic factors for OS were pre-operative metastases (P=0.0001), tumour location (P=0.0048), type of chemotherapy (P=0.002) and response to chemotherapy (P=0.0004). Chemotherapy (P=0.037), tumour location (P=0.0017) and metastases at diagnosis (P=0.0025) were significant. CONCLUSION: The most effective treatment of Ewing's sarcoma is chemotherapy.

Adolescent↗

Long-term followup of uncemented tumor endoprostheses for the lower extremity.

Between 1982 and 1989, 100 primary lower limb reconstructions were done using the Kotz Modular Femur Tibia Reconstruction System after resection of a malignant tumor. In 32 patients a proximal femur prosthesis was implanted, in 40 patients a distal femur prosthesis was implanted, in 19 patients a proximal tibia component was implanted, in four patients a total femur prosthesis was implanted, and in five patients a total knee prosthesis was implanted. The Kaplan-Meier estimate of the overall survival rate of the prostheses was 85% after 3 years, 79% after 5 years, and 71% after 10 years. The most common reason for implant failure was aseptic loosening in 27% of patients (11 patients; range, 10-121 months) after the initial operation. The other reasons for revision surgery were implant fracture (n 5 4) and infection (n 5 4). Early repair of prostheses-related minor complications, such as worn polyethylene bushings, resulted in a statistically significant reduction of implant failure. After a median followup of 127.5 months after the initial surgery, 51 patients had died and eight patients were lost to followup. Forty-one patients were evaluated clinically and radiologically using the Musculoskeletal Tumor Society score and the radiologic implant evaluation system of the International Symposium on Limb Salvage; these 41 patients had a mean of 80% (range, 40%-100%) of the normal functional capability.

Adult↗

The role of surgery and resection margins in the treatment of Ewing's sarcoma.

Because of the enormous progress in surgery in the treatment of patients with tumors, the current study analyzed the influence of wide surgical resection margins on the outcome of patients with Ewing's sarcoma. Between 1980 and 1994, 86 patients were treated with systemic therapy and surgery (biopsy in six patients, tumor resection in 80 patients). Forty-four patients also had radiation therapy. The 5-year overall survival was 56.8% (5-year disease-free survival, 59.4%). The 5-year overall survival after radical or wide resection was 60.2% (5-year disease-free survival, 58.2%), in comparison with 40.1% (46.7%) after marginal or intralesional resection. Two patients with inadequate resection margins had local recurrences. In addition to the influence of neoadjuvant chemotherapy for higher survival rates (5-year overall survival with a good response was 80.2% versus 41.7% with a poor response), adequate surgical margins significantly affect the outcome for patients with Ewing's sarcoma.

Adolescent↗

Local tumor control and morbidity after one to three fractions of stereotactic external beam irradiation for uveal melanoma.

BACKGROUND AND PURPOSE: To evaluate prospectively local tumor control and morbidity after 1-3 fractions of stereotactic external beam irradiation (SEBI) in patients with uveal melanoma, unsuitable for ruthenium-106 brachytherapy or local resection. MATERIAL AND METHODS: This phase I/II study includes 62 selected patients with uveal melanoma. The mean initial tumor height was 7.8+/-2.8 mm. With the Leskell gamma knife SEBI, 41 patients (66%) were irradiated with two equal fractions of 35, 30 or 25 Gy/fraction, 14 patients (22%) were treated with three fractions of 15 Gy each, and seven patients (11%) with small tumor volumes below 400 mm(3) were treated with one fraction of 45 Gy. The mean total dose was 54+/-8 Gy. The minimal follow-up period was 12 months, and the median follow-up was 28.3 months. Data on radiation-induced side-effects were analyzed with the Cox proportional hazards model for possible risk factors. RESULTS: Local tumor control was achieved in 98% and tumor height reduction in 97%. The mean relative tumor volume reductions were 44, 60 and 72% after 12, 24 and 36 months, respectively. Seven patients developed metastases (11%). Secondary enucleation was performed in eight eyes (13%). Morbidity was significant in tumors exceeding 8 mm in initial height; it was comparable and acceptable in those smaller. In the stepwise multiple Cox model, tumor localization, height and volume, planning target volume (PTV), total dose and patient age were identified as the strongest risk factors for radiation-induced lens opacities, secondary glaucoma, uveitis, eyelash loss and exudative retinal detachment. In this model, the high-dose volume irradiated with more than 10 Gy/fraction was the strongest risk factor for radiation-induced uveitis. CONCLUSIONS: Stereotactic external photon beam irradiation and a total dose of 45-70 Gy delivered in one to three fractions are highly effective at achieving local tumor control in uveal melanoma. Further clinical studies using smaller fraction doses, and consequent smaller high-dose volumes, are justified to optimize dose and fractionation. Fractionated stereotactic irradiation has a challenging potential as an eye-preserving treatment in uveal melanoma.

Adult↗

Using SAS to calculate the Kent and O'Quigley measure of dependence for Cox proportional hazards regression model.

Kent and O'Quigley (1988) apply the concept of information gain to define a measure of dependence (R-squared measure) between explanatory variables and a censored response variable within the framework of the Cox model. Two SAS macros to calculate this measure are presented. The first one is based on a Newton-Raphson search and makes use of the SAS IML procedure. The second one is a simple grid search using SAS DATA steps and Base-SAS procedures.

Data Interpretation, Statistical↗

Drug resistance factors in acute myeloid leukemia: a comparative analysis.

To compare the clinical relevance of drug resistance factors in de novo acute myeloid leukemia (AML), we determined their relationship to both response to induction chemotherapy and survival of the patients in univariate as well as multivariate analyses. The drug resistance factors immunocytochemically studied in 111 patients at the time of diagnosis included the lung resistance protein (LRP), P-glycoprotein (P-gp), multidrug resistance protein (MRP1) and bcl-2. In the univariate analyses, age (P = 0.005), karyotype (P = 0.03), LRP (P = 0.003), P-gp (P = 0.02) and bcl-2 (P = 0.03) predicted for response to induction chemotherapy, whereas MRP1 had no predictive value. Age (P = 0.05), karyotype (P = 0.05) and LRP (P = 0.03) retained their predictive value in the multivariate logistic regression analyses. With regard to overall survival, age (P = 0. 008), karyotype (P = 0.006), LRP (P = 0.001) and P-gp (P = 0.01) were of prognostic value in the univariate Cox regression analyses but only age (P = 0.01), karyotype (P = 0.02) and LRP (P = 0.01) retained their prognostic significance in the multivariate analyses. A risk score based on the number of independent prognostic factors allowed division of patients into four groups with different outcome. In these groups, the complete remission rates were 93%, 75%, 47% and 33%, respectively, and median overall survival was 2.4, 1.2, 0.6 and 0.2 years, respectively. Thus, several drug resistance factors did predict outcome in the univariate analyses but LRP was the only drug resistance factor with independent predictive and prognostic significance. The proposed risk score might be useful for risk-adapted treatment in the future. Leukemia (2000) 14, 68-76.

Acute Disease↗

Cardiac autonomic function in patients suffering from primary focal hyperhidrosis.

Cardiac autonomic function in patients (n = 63) with primary focal hyperhidrosis and healthy controls (n = 28) was investigated by short-term frequency domain power spectral analysis of heart rate variability. The power of the very-low-frequency band (0.01-0.05 Hz) was significantly lower in patients with axillary hyperhidrosis than in controls. No differences between groups could be observed at investigation of the low-frequency band (0.05-0.15 Hz), which was a surprising finding because this band represents also sympathetic cardiac innervation. At the high-frequency band (0.15-0.5 Hz), which represents parasympathetic cardiac innervation, an interaction of type and position influencing spectral power was detected. Our highly interesting findings indicate that primary focal hyperhidrosis is based on a much more complex autonomic dysfunction than generalised sympathetic overactivity and seems to involve the parasympathetic nervous system as well.

Adult↗

Clinical relevance of the lung resistance protein in diffuse large B-cell lymphomas.

Drug resistance of non-Hodgkin's lymphomas may involve mechanisms of the multidrug resistance phenotype including the lung resistance protein (LRP) and the multidrug resistance protein (MRP1). To determine the clinical relevance of these multidrug resistance factors in previously untreated diffuse large B-cell lymphomas (n = 48), we studied LRP and MRP1 expression in lymphoma cells and their impact on clinical outcome. LRP and MRP1 expression were immunohistochemically assessed by means of the monoclonal antibodies LRP-56 and MRPr1, respectively. LRP was positive in 23% and MRP1 in 44% of the samples. LRP expression was associated with higher tumor stage (P = 0.03), elevated serum lactate dehydrogenase levels (P = 0.01), and the International Prognostic Index (P = 0.0001). LRP-positive patients had a lower complete response rate to polychemotherapy than LRP-negative patients (18 versus 65%; P = 0.006). Patients with LRP expression had a shorter overall survival than those without LRP expression (median of 0.9 years versus median not reached; P = 0.001). MRP1 expression was independent of clinical and laboratory parameters and had no impact on the outcome of chemotherapy or survival of the patients. These data suggest that LRP expression but not MRP1 expression is an important mechanism of drug resistance associated with worse clinical outcome in previously untreated diffuse large B-cell lymphomas. Thus, the reversal of LRP-mediated drug resistance may improve clinical outcome in diffuse large B-cell lymphoma in the future.

ATP-Binding Cassette Transporters↗

CA 125 regression after two completed cycles of chemotherapy: lack of prediction for long-term survival in patients with advanced ovarian cancer.

The prognostic influence of CA 125 regression between the time point before surgery and after two completed courses of chemotherapy was studied in 210 patients with advanced ovarian cancer, and was compared to other well established prognostic factors. CA 125 blood samples were collected preoperatively (CA 125 pre) and 3 months after surgery (CA 125 3 mo) (at the beginning of the 3rd cycle of chemotherapy). The parameter CA 125 regression defined as log10 (CA 125 3 mo/CA 125 pre) was used for statistical analysis. In a survival analysis using a Cox proportional hazards model, CA 125 regression (P = 0.0001), residual tumour (P = 0.0001), age (P = 0.0095) and grading (P = 0.044) were independent variables, whereas stage of disease, histology, ascites and type of surgery failed to retain significance. Using log10 (CA 125 3 mo/CA 125 pre) as simple covariate in a Cox model showed a hazard ratio of 1.70 (95% confidence interval 1.32-2.19, P = 0.0001). However, a detailed analysis of the interaction of time with the prognostic factor CA 125 regression on survival revealed a strong time-dependent effect with a hazard ratio of more than 6 immediately after two courses of chemotherapy, whereas within approximately 1 year the hazard ratio for the surviving patients dropped quickly to the neutral level of 1. In summary, CA 125 regression is an independent prognostic factor for survival of women with advanced ovarian cancer and allows an identification of a high-risk population among patients with advanced ovarian cancer. However, the discriminating power of serial CA 125 for long-term survival seems to be temporary and prediction of individual patients outcome is far less precise.

Adult↗

Induction of complete wound healing in recalcitrant ulcers by low-intensity laser irradiation depends on ulcer cause and size.

Chronic skin ulcers still represent a therapeutic challenge in dermatology. Among the various non-invasive treatment modalities used for the improvement of impaired wound healing, low-intensity laser irradiations are gaining an increasing body of interest. We used low-intensity laser irradiations delivered by a 30 mW helium-neon laser at an energy density of 30 J/cm2 three times weekly for the induction of wound healing in ulcers of diverse causes. Twenty patients with the same number of ulcers, which had previously been treated by conventional wound care for a median period of 34 weeks (range: 3-120 weeks) without any significant evidence of healing, were included in the study. Concerning the underlying disorders, patients were divided into four groups: diabetes, arterial insufficiency, radio damage and autoimmune vasculitis. In all ulcers, complete epithelization could be induced by laser therapy. No amputation or any other surgical intervention was necessary and no adverse effects of any kind were noted during low-intensity laser treatment. Regarding the different diagnoses, a statistically significant difference was noted (P = 0.008): ulcers due to radio damage healed significantly faster than those caused by diabetes (6 weeks [range: 3-10 weeks] vs. 16 weeks [range: 9-45 weeks], P = 0.005). Wound healing in autoimmune vasculitis (24 weeks [range: 20-35 weeks]) required longer than in radiodermitis, although the difference was not significant. In addition to the diagnosis, wound size was found to be an important factor influencing the duration of wound closure (P = 0.028), whereas duration of previous conventional treatment (P = 0.24) and depth (P = 0.14) showed no effect. Our results indicate that low-intensity laser irradiation could be a valuable non-invasive tool for the induction of wound healing in recalcitrant ulcers, and that healing time is correlated with the ulcer cause and size.

Adult↗

Local and systemic control after ablative and limb sparing surgery in patients with osteosarcoma.

Limb salvage surgery in patients with osteosarcoma is reported to cause a higher rate of local recurrences with a poorer chance of survival. It was the aim of the study to analyze differences between ablative and limb sparing surgery in patients with osteosarcoma who are treated with chemotherapy with respect to local and systemic tumor control and to determine independent prognostic factors. One hundred thirty consecutive patients younger than the age of 21 years who were operated on at the authors' institution for osteosarcoma of the extremities were reviewed. Histologic evaluations of surgical margins according to Enneking and coworkers revealed mostly wide (n = 109) and radical (n = 10) resection margins. The 5-year disease free survival rate was 60% for those patients treated by amputation and 71% for those treated by limb salvage. The overall local recurrence rate was 2.3%; 4.3% for ablation but only 1.2% for limb sparing surgeries. Multivariate analysis showed an independent effect of tumor volume, response to chemotherapy, and as expected, metastases at the time of diagnosis on overall survival. These data indicate that in patients where wide or radical tumor resection can be achieved, no difference in the outcome between ablative and limb sparing surgery occurred in local and systemic tumor control.

Adolescent↗

[Cytokeratin tumor markers in ovarian carcinoma: tissue polypeptide specific antigen (TPS) and M3/M21].

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin tumor marker M3/M21 as a screening, prognostic, and monitoring marker for ovarian cancer and as a predictive marker in patients with adnexal masses. In order to determine the specificity of the M3/M21 test we investigated M3/M21 serum levels in several benign conditions. The cytokeratin tumor markers M3/M21 and Tissue Polypeptide Specific Antigen (TPS) were also investigated in the follow-up of ovarian cancer patients. We evaluated M3/M21 serum levels in 75 patients suffering from ovarian cancer FIGO stages Ia to III, using a prototype immunoradiometric assay (IRMA). Sera of patients with benign cysts, endometriosis, pelvic inflammatory disease, inflammatory bowel disease and liver cirrhosis were evaluated in 90, 10, 38, 10, and 20 cases, respectively. Furthermore, we analyzed TPS serum levels by means of IRMA during the follow-up of 40 patients suffering from ovarian cancer. With a sensitivity of 57% and a specificity of 95% M3/M21 was not suitable as a screening marker for ovarian cancer. Although M3/M21 was able to discriminate between ovarian cancer and benign adnexal tumors (univariate logistic regression, p = 0.0003), M3/M21 did not provide additional information (in addition to CA 125) (multivariate logistic regression, p = 0.2). M3/M21 serum levels were elevated in several benign conditions such as liver cirrhosis and inflammatory bowel disease. In ovarian cancer patients elevated M3/M21 serum levels prior to therapy were associated with a poor overall and disease-free survival (log-rank test, p = 0.03, and log-rank test, p = 0.01, respectively). In patients with recurrent ovarian cancer M3/M21 and TPS showed median lead-time effects of 3.2 and 3.9 months, respectively. M3/M21, while obviously not suitable for screening or differential diagnosis of adnexal masses, could be useful as an additional prognostic factor. M3/M21 and TPS are valuable tumor markers in the follow-up of ovarian cancer patients.

Adult↗